Characterization of genetic variants in children with refractory epilepsy / 中华医学遗传学杂志

OBJECTIVE@#To analyze the characteristics of genetic variants among children with refractory epilepsy (RE).@*METHODS@#One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed.@*RESULTS@#In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ2 = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ2 = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references.@*CONCLUSION@#28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.

Lineage reprogramming of fibroblasts into induced cardiac progenitor cells by CRISPR/Cas9-based transcriptional activators

Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Here we show lineage reprogramming to iCPCs through a dead Cas9 (dCas9)-based transcription activation system. Targeted and robust activation of endogenous cardiac factors, including GATA4, HAND2, MEF2C and TBX5 (G, H, M and T; GHMT), can reprogram human fibroblasts toward iCPCs. The iCPCs show potentials to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells . Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming. Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling, drug discovery and individualized cardiac cell therapy.

Develop of an intelligent cabinet with constant temperature and adjustable height and its application / 中国实用护理杂志

Objective To develop an intelligent cabinet with constant temperature and adjustable height,which is safer,more scientific and comfortable for heat preservation after surgical operation.Methods According to the demands of microscopic surgery we analyzed the disadvantages of existing equipment in order to seek new materials to solve the current problems.Results Using nanometer electric heating film to control temperature at 30～35 ℃ and adjust temperature in this range.Moreover debugging angle of stainless steel adjustable upholder at 0～45°.Conclusions Nanometer electric heating film is a kind of high safety,reliability and strong stability heating material and can be used for the microscopic surgery insulation.Adjustable lifting upholder makes limbs more comfortable with freely height.It shows that setting temperature at 30～31℃,angel value at 20～25°would be relatively suitable after our experiment.

Study on the cytosine deaminases expression in human immunodeficiency virus-1 infected patients / 中华传染病杂志

Objective To quantitatively investigate the expression levels of the cytosine deaminases,hA3B,hA3F and hA3G in peripheral blood mononuclear cell(PBMC)of human immunodeficiency virus(HIV)infected patients and to analyze the correlation between cytosine deaminases expression and CD4~+ T lymphocyte counts. Methods Peripheral blood samples were collected from 21 HIV-infected subjects who didn't take antiretroviral therapy(ART-),21 HIV-infected subjects receiving ART(ART+),and 10 HIV-uninfected subjects. PBMC were isolated by Ficoll density gradient centrifugation, followed by RNA extraction and cDNA synthesis.hA3B,hA3F and hA3G mRNA levels were determined by real-time fluorescent quantitative polymerase chain reaction(PCR).CD4~+ T lymphocyte counts were determined using flow cytometry. Data were analyzed by t test, t' test or Wilcoxon rank sum test. Results In HIV-infected subjects without or with ART,HIV-uninfected subjects, the levels of hA3B mRNA were 208.4,365.2 and 563.6,hA3F mRNA were 245.5,316.6 and 442.9,hA3G mRNA were 404.6,360.8 and 638.6,respectively.hA3G mRNA level in HIV-infected subjects was lower than that in HIV-uninfected controls(P=0.0131),but there was no statistical difference between ART+ and ART-groups(P=0.7342).There were no correlations between hA3B,hA3F and hA3G mRNA levels and CD4+ T lymphocyte counts in either ART-or ART+HIV-infected subjects(ART-:r=-0.0104,r=-0.0545,r=0.1623,all P＞0.05;ART+:r=0.3220,r=0.2193,r=0.1455,all P＞0.05).In addition,hA3B,hA3F and hA3G mRNA levels were positively correlated with one another in ART-HIV-infected subjects and HIV-uninfected controls(P＜0.05),but not in ART-HIV-infected subjects(P＞0.05).Conclusions hA3B,hA3F and hA3G expression levels do not directly correlate with CD4~+ T lymphocyte counts in HIV-1-infected patients,hA3B,hA3F and hA3G expression levels in PBMCs tend to he decreased after HIV-1 infection, and ART may increase hA3B and hA3F mRNA expression.

The causes of death for 89 HIV/AIDS patients / 中华临床感染病杂志

Objective To analyze the causes of death for 89 HIV/AIDS patients,and the association of CD4+ T lymphocyte counts with the mortality.Methods Data were collected from 89 deceasedpatients who were admitted to Shanghai Public Health Clinical Center from Jan 1996 to Sep 2007,and wereretrospectively analyzed with t-test.Results Heterosexual,blood transfusion and blood products were themajor transmission routs for 89 deceased HIV/AIDS patients.The primary causes of death varied with different levels of CD4+ T lymphocyte counts.With higher CD4+T lymphocyte counts,patients were more likelyto die from non-AIDS-related opportunistic infections such as upper digestive tract hemorrhage.Serious pulmonary infection induced by various etiologies was the primary cause of death.Co-infections of multiple etiologics were often seen in these death cases.Conclusion Opportunistic infection is the primary cause of death for HIV/AIDS patients.Appropriate therapies should be based on CD4+ T lymphocyte counts and patients' specific conditions to reduce the mortality.